CARBOPLATIN COMBINED WITH AMIFOSTINE, A BONE-MARROW PROTECTANT, IN THE TREATMENT OF NON-SMALL-CELL LUNG-CANCER - A RANDOMIZED PHASE-II STUDY
CARBOPLATIN COMBINED WITH AMIFOSTINE, A BONE-MARROW PROTECTANT, IN THE TREATMENT OF NON-SMALL-CELL LUNG-CANCER - A RANDOMIZED PHASE-II STUDY
复制标题
DOI：
10.1038/bjc.1995.546
复制
发表时间：
1995-12-01
影响因子：
8.8
通讯作者：
THATCHER, N
中科院分区：
文献类型：
--
作者：
BETTICHER, DC;ANDERSON, H;THATCHER, N
氨磷汀（WR-2721）是一种硫醇化合物，已被证明可以保护正常组织免受烷基化剂和顺铂引起的毒性的影响，而不会丧失抗肿瘤作用。为了证实这一结果，我们进行了一项II期随机试验，以确定在不能手术的非小细胞肺癌（NSCLC）患者中，氨磷汀的加入是否降低了卡铂的毒性，同时又不丧失抗肿瘤活性。在第一疗程卡铂（600 mg m（-2）静脉输注）后，21名患者被随机分配接受3个周期的单卡铂（C组）或3次910 mg m（-2）氨磷汀（CA组）输注，间隔28天。氨磷汀于卡铂前20分钟、卡铂后2小时和4小时给予。由于910 mg m（-2）氨磷汀输注导致6例患者低血压，其他4例患者的剂量减少了25%，为683mg m(-2) t.i.d。氨磷汀在这个剂量水平下耐受性良好。CA组的5名患者和C组的3名患者由于疾病进展（n = 3）、氨磷汀副作用（低血压、打喷嚏和生病，n = 4）和卡铂诱导的血小板减少症（n = 1）而停止了原计划的治疗。在研究开始时和随机化前卡铂第一个疗程后，两个治疗组的骨髓和肾功能相似。将卡铂+氨磷汀20个疗程与单独卡铂25个疗程进行比较。虽然两组在血液学值方面没有统计学上的显著差异，但CA组血小板恢复的中位时间（100 × 10(9) l-L）（13.5天vs 21天，P = 0.04）以及静脉注射抗生素和其他支持性治疗的住院需求倾向于减少（0/20 vs 6/25患者疗程，P = 0.06）。排除氨磷汀的肿瘤保护作用，有效率和中位生存期（14个月vs 9个月）没有差异。这些少数患者的结果表明，氨磷汀与卡铂联合用药可能减少血小板减少症和住院时间。
Amifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m(-2) i.v. infusion), 21 patients were randomised to receive three cycles of carboplatin alone (C arm) or three infusions of amifostine at 910 mg m(-2) (CA arm) at 28 day intervals. The amifostine was given 20 min before and at 2 and 4h after carboplatin. Since the 910 mg m(-2) amifostine infusion led to hypotension in six patients, the dosage was reduced by 25%, to 683 mg m(-2) t.i.d., in the other four patients. Amifostine was well tolerated at this dose level. Five patients in the CA arm and three in the C arm had their planned treatment discontinued owing to progressive disease (n = 3), amifostine side-effects (hypotension, sneezing and sickness, n = 4), and carboplatin-induced thrombocytopenia (n = 1). Bone marrow and renal function at study entry and after the first course of carboplatin before randomisation were similar in both treatment arms. Twenty courses of carboplatin + amifostine have been compared with 25 courses of carboplatin alone. Although there was no statistically significant difference with respect to haematological values comparing both arms, the median time to platelet recovery (>100 x 10(9) l-L) (13.5 days vs 21 days; P = 0.04) and the need for hospitalisation for i.v. antibiotic and other supportive treatment tended to be reduced in the CA arm (0/20 vs 6/25 patient courses; P = 0.06). Response rates and median survival (14 vs 9 months) were no different, excluding tumour protection activity by amifostine. These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation.